Accuracy of preoperative automatic measurement of the liver volume by CT-scan combined to a 3D virtual surgical planning software (3DVSP)

Background

Liver volumetry is a critical component of safe hepatic surgery, in order to minimize the risk of postoperative liver failure. Liver volumes can be calculated routinely using the time-consuming gold standard method of manual volumetry. The current work sought to evaluate an alternative automatic technique based on a novel 3D virtual planning software, and to compare it to the manual technique.

Methods

A prospective study of patients undergoing liver resection was conducted. Every patient had a pre and 2-day postoperative CT-scan. For each patient, total, remnant and resected volumes were calculated manually and automatically. Planes of resection were verified by a hepatobiliary surgeon and compared with postoperative volumes. Paired t-tests and correlation coefficients were calculated.

Results

A major hepatectomy was carried out in 36/43 patients. The automatic TLV (1,759 mL) and the manual TLV (1,832 mL) were significantly different (p < 0.001), but extremely highly correlated (r = 0.989). The percentages of preoperative RLV (manual 58.5 %, automatic 58.9 %) were similar, with an excellent correlation of 0.917. The preoperative RLV were matched with the 2-day postoperative RLV showing a significant difference (p = 0.0301). The resected volumes using both techniques (871 and 832 mL) were compared with the resected specimen volume (670 mL), showing a significant difference (p < 0.001) but a high degree of correlation (r = 0.874).

Conclusion

The 3D virtual surgical planning software is accurate and reliable in determining the total liver and future remnant liver volumes. This technique demonstrates a good correlation with the manual technique. Future work will be required to confirm these findings and to evaluate the clinical value of the three-dimensional planning platform.     

One-stage Resection for Bismuth Type IV Hilar Cholangiocarcinoma with High Hilar Resection and Parenchyma-preserving Strategies: A Cohort Study

Background

Bismuth type IV hilar cholangiocarcinoma (HC) tumors are usually considered unresectable. The strategies of high hilar resection while preserving liver parenchyma can achieve potentially one-stage curative resection for this condition. The aim of the present study was to investigate the feasibility and safety of available strategies.

Methods

Fifty-one consecutive patients with bismuth type IV HC who underwent one-stage resection were retrospectively reviewed with regard to curative resection rate, remnant liver volume, morbidity, mortality, and survival time.

Results

The total median survival time was 29 months. The R₀ (curative resection) rate was 57.8 %. The ratio of the remnant liver volume (RLV) to the standard liver volume (SLV) ranged from 35.0 to 60.6 %, with a mean of 44.5 %. The in-hospital mortality and morbidity rates were 3.9 and 37.2 %, respectively. In the R₀ patients’ survival, there was not a significant difference between bilioenteric anastomosis and hepatoenteric anastomosis (P = 0.714).

Conclusions

Combined caudate lobe and high hilar resection (CCHR) is technically safe and oncologically justifiable and could be adopted with a high cure rate as a one-stage resection procedure for most patients with Bismuth type IV HC whose total bilirubin level is less than 20 mg/L and whose direct bilirubin is more than 60 % of total bilirubin.     

Perioperative Complications After Neoadjuvant Chemotherapy With and Without Bevacizumab for Colorectal Liver Metastases

Purpose

Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM).

Methods

Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n?=?134), or chemotherapy alone (group 2, n?=?57). We compared demographics, surgical characteristics, and perioperative course.

Results

Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p?=?0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p?=?0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p?=?0.56.

Conclusion

Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.     

Effects of different pressure levels of CO2 pneumoperitoneum on liver regeneration after liver resection in a rat model

Background

A recent study demonstrated that high pressure of carbon dioxide (CO₂) pneumoperitoneum before liver resection impairs postoperative liver regeneration. This study was aimed to investigate effects of varying insufflation pressures of CO₂ pneumoperitoneum on liver regeneration using a rat model.

Methods

180 male Wistar rats were randomly divided into three groups: control group (without preoperative pneumoperitoneum), low-pressure group (with preoperative pneumoperitoneum at 5 mmHg), and high-pressure group (with preoperative pneumoperitoneum at 10 mmHg). After pneumoperitoneum, all rats were subjected to 70 % partial hepatic resection and then euthanized at 0 min, 12 h, and on postoperative days (PODs) 1, 2, 4, and 7. Following outcome parameters were used: liver regeneration (liver regeneration rate, mitotic count, Ki-67 labeling index), hepatocellular damage (serum aminotransferases), oxidative stress [serum malondialdehyde (MDA)], interleukin-6 (IL-6), and hepatocyte growth factor (HGF) expression in the liver tissue.

Results

No significant differences were observed for all parameters between control and low-pressure groups. The liver regeneration rate and mitotic count were significantly decreased in the high-pressure group than in control and low-pressure groups on PODs 2 and 4. Postoperative hepatocellular damage was significantly greater in the high-pressure group on PODs 1, 2, 4, and 7 compared with control and/or low-pressure groups. Serum MDA levels were significantly higher in the high-pressure group on PODs 1 and 2, and serum IL-6 levels were significantly higher in the high-pressure group at 12 h and on POD 1, compared with control and/or low-pressure groups. The HGF tissue expression was significantly lower in the high-pressure group at 12 h and on PODs 1 and 4, compared with that in control and/or low-pressure groups.

Conclusions

High-pressure pneumoperitoneum before 70 % liver resection impairs postoperative liver regeneration, but low-pressure pneumoperitoneum has no adverse effects. This study suggests that following laparoscopic liver resection using appropriate pneumoperitoneum pressure, no impairment of liver regeneration occurs.     

Impact of Perioperative Phosphorus and Glucose Levels on Liver Regeneration and Long-term Outcomes after Major Liver Resection

Introduction

The impact of phosphorus as well as glycemic alterations on liver regeneration has not been directly examined. We sought to determine the impact of phosphorus and glucose on liver regeneration after major hepatectomy.

Methods

Early and late liver regeneration index was defined as the relative increase of liver volume (RLV) within 2[(RLV_2m-RLV_p)/RLV_p] and 7 months[(RLV_7m-RLV_p)/RLV_p] following surgery. The association of perioperative metabolic factors, liver regeneration, and outcomes was assessed.

Results

On postoperative day 2, 50 (52.6 %) patients had a low phosphorus level (≤2.4 mg/dl), while 45 (47.4 %) had a normal/high phosphorus level (>2.4 mg/dl). Despite comparable clinicopathologic characteristics (all P?>?0.05) and RLV/TLV at surgery (P?=?0.84), regeneration index within 2 months was lower in the normal/high phosphorus group (P?=?0.01) with these patients having increased risk for postoperative liver failure (P?=?0.01). The inhibition of liver regeneration persisted at 7 months (P?=?0.007) and was associated with a worse survival (P?=?0.02). Preoperative hypoglycemia was associated only with a lower early regeneration index (P?=?0.02).

Conclusions

Normal/high phosphorus was associated with inhibition of early and late liver regeneration, as well as with an increased risk of liver failure and worse long-term outcomes. Immediate preoperative hypoglycemia was associated with a lower early volumetric gain. Metabolic factors may represent early indicators of liver failure that could identify patients at increased risk for worse outcomes.

     

The feasibility and potential benefit of preoperative chemotherapy for colorectal liver metastasis (CLM): a single-centered retrospective study

Purposes

The benefit of neo-adjuvant chemotherapy for liver-limited metastatic colorectal cancer is still controversial. This study defined the resectability regardless of the size and number of liver metastases, and attempted curative hepatic resection in all cases.

Methods

Sixty-four patients that tolerated chemotherapy were diagnosed with CLM (colorectal liver metastases) without extrahepatic metastase from January 2007 to November 2010, and received an oxaliplatin-based regimen. This study assessed the resectability after chemotherapy, and the patients were divided in two groups; the resected and unresected group. Sixteen patients underwent hepatic resection without chemotherapy.

Results

Thirty-five patients underwent surgical resection (resected group) and twenty-nine patients were considered unresectable (unresected group). All 35 patients in the resected group safely received oxaliplatin-based chemotherapy safely without serious adverse effects. No serious postoperative complications were observed. The median overall survival (MST) was significantly higher in the resected than in the unresected group (56.93 [95 % CI 38.13–75.73] and 25.07 months [95 % CI 17.87–32.26], respectively; P < 0.001). The median disease-free survival was 20.2 [95 % CI 8.82–31.65] months in the resected group.

Conclusion

Preoperative chemotherapy for CLM is well tolerated and does not increase postoperative complications. Curative surgery with preoperative chemotherapy has the potential to improve the overall survival in patients with CLM.     

Percentage of Future Liver Remnant Volume Before Portal Vein Embolization Influences the Degree of Liver Regeneration After Hepatectomy

Background

Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration.

Methods

Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis.

Results

PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm³, respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r?=?0.63, p?<?0.0001). Multiple regression analysis showed that only %FLR-pre was independently correlated with posthepatectomy liver regeneration (p?=?0.027, odds ratio?=?13.8).

Conclusion

After PVE and the subsequent hepatectomy, liver regeneration was accomplished in a two-step manner. Liver regeneration was strongly influenced by the %FLR-pre.     

Usefulness of Contrast-Enhanced Intraoperative Ultrasonography (CE-IOUS) in Patients with Colorectal Liver Metastases after Preoperative Chemotherapy

Aims

The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques.

Methods

From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography.

Results

Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n?=?9), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n?=?4), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p?=?0.047), resolution of at least one metastasis (p?=?0.011), and small liver metastases (largest lesion size ≤20 mm) after chemotherapy (p?=?0.007).

Conclusion

In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate.     

Safety of Liver Resection in the Elderly: How Important Is Age?

Background

With the aging population, more elderly patients are being considered for hepatic resection. We investigated whether advanced age was associated with higher rate and severity of postoperative complications.

Methods

A total of 75 patients aged ≥70 years (group E) were matched with 75 patients aged <70 years (group Y) by the extent of liver resection and by operative indications. Primary outcome measures were rates and severity of complications. Secondary outcome measures were length of hospital stay and discharge destination. Univariate analysis was also performed to identify variables associated with higher surgical risk.

Results

Male-to-female ratio was 43:32 in both groups. Overall complication rates were 44 and 33.3% in group E and Y, respectively (P = 0.241; odds ratio = 1.57; 95% confidence interval [95% CI], 0.81–3.05). There was no mortality in both groups. The only postoperative age-related morbidity was confusion in the elderly. There was no difference in the rates of severe complications (grade ≥3) between group E and group Y (16 vs. 14.7%; P = 0.744; odds ratio = 1.11; 95% CI, 0.46–2.70). Median length of hospital stay were 7 and 6 days, respectively (P = 0.01). Nineteen percent and 1% of patients in group E and group Y were discharge to rehabilitation facilities, respectively (P = 0.001). Univariate analysis showed that preoperative systemic chemotherapy and longer operative time were associated with higher morbidity in the elderly.

Conclusions

Liver resection can be performed in patients aged ≥70 years as safely as in younger patients. Duration and timing of systemic chemotherapy before liver resection should be optimized to minimize postoperative morbidity.     

Can Plasma Bile Salt, Triglycerides, and apoA-V Levels Predict Liver Regeneration?

Background

Preoperative portal vein embolization (PVE) is used to increase the future remnant liver (FRL) in patients requiring extensive liver resection. Computed tomography (CT) volumetry, performed not earlier than 3–6 weeks after PVE, is commonly employed to assess hypertrophy of the FRL following PVE. Early parameters to predict effective hypertrophy are therefore desirable. The aim of the present study was to assess plasma bile salt levels, triglycerides (TG), and apoA-V in the prediction of the hypertrophy response during liver regeneration.

Methods

Serum bile salt, TG, and apoA-V levels were determined in 20 patients with colorectal metastases before PVE, and 5 h, 1, and 21 days after PVE, as well as prior to and after (day 1–7, and day 21) subsequent liver resection. These parameters were correlated with liver volume as measured by CT volumetry (%FRL-V), and liver function was determined by technetium-labeled mebrofenin hepatobiliary scintigraphy using single photon emission computed tomography.

Results

Triglyceride levels at baseline correlate with volume increase of the future remnant liver (FRL-V) post-PVE. Also, bile salts and TG 5 h after PVE positively correlated with the increase in FRL volume (r = 0.672, p = 0.024; r = 0.620, p = 0.042, resp.) and liver function after 3 weeks (for bile salts r = 0.640, p = 0.046). Following liver surgery, TG levels at 5 h and 1 day after resection were associated with liver remnant volume after 3 months (r = 0.921, p = 0.026 and r = 0.981, p = 0.019, resp). Plasma apoA-V was increased during liver regeneration.

Conclusions

Bile salt and TG levels at 5 h after PVE/resection are significant early predictors of liver volume and functional increase. It is suggested that these parameters can be used for early timing of volume assessment and resection after PVE.     

Metabolic Response to Preoperative Chemotherapy Predicts Prognosis for Patients Undergoing Surgical Resection of Colorectal Cancer Metastatic to the Liver

Background

Biological characteristics of colorectal cancer liver metastases (CRCLM) are increasingly recognized as major determinants of patient outcome. The purpose of this study was to evaluate the prognostic value of metabolic response to preoperative chemotherapy as quantified by ¹⁸F-FDG positron emission tomography (PET) for patients undergoing liver resection of CRCLM.

Methods

All patients (n = 80) who had staging PET before liver resection for CRCLM at Austin Health in Melbourne between 2004 and 2011 were included. Thirty-seven patients had PET and CT imaging before and after preoperative chemotherapy. Semiquantitative PET parameters—maximum standardized uptake variable (SUV_max), metabolic tumour volume (MTV), and total glycolytic volume (TGV)—were derived. Metabolic response was determined by the proportional change in PET parameters (?SUV_max, ?MTV, ?TGV). Prognostic scores, CT RECIST response, and tumour regression grading (TRG) were also assessed. Correlation to recurrence-free (RFS) and overall survival (OS) was assessed using Kaplan–Meier survival and multivariate analysis.

Results

Semiquantitative parameters on staging PET before chemotherapy were not predictive of prognosis, whereas all parameters after chemotherapy were prognostic for RFS and OS. Only ?SUV_max was predictive of RFS and OS on multivariate analysis. Patients with metabolically responsive tumours had an OS of 86 % at 3 years vs. 38 % with nonresponsive or progressive tumours (p = 0.003). RECIST and TRG did not predict outcome.

Conclusions

Tumour metabolic response to preoperative chemotherapy as quantified by PET is predictive of prognosis in patients undergoing resection of CRCLM. Assessing metabolic response uniquely characterizes tumour biology, which may allow future optimization of patient and treatment selection.     

Evaluation of the Usefulness of the Indocyanine Green Clearance Test for Chemotherapy-Associated Liver Injury in Patients with Colorectal Cancer Liver Metastasis

Background

The indocyanine green (ICG) clearance test is reported to be useful for the preoperative evaluation of hepatic functional reserve. However, the ICG clearance test has not been sufficiently investigated in patients with colorectal liver metastasis after chemotherapy. The aim of the present study was to evaluate whether the ICG clearance test is a useful parameter for the preoperative detection of chemotherapy-associated liver injury.

Methods

Ninety-four patients undergoing liver resection for colorectal liver metastasis after chemotherapy were studied. The medical records for each case were retrospectively reviewed. They underwent pathological assessment to clarify the degree of histopathological liver injury of the nontumoral liver parenchyma. In addition, the correlation between the pathological score and the ICG retention rate at 15 min (ICG-R15) was analyzed.

Results

Sinusoidal injury was observed in the 31 of 94 patients. Steatohepatitis was observed in the 40 of 94 patients. There was no strong correlation between the preoperative ICG-R15 value and the sinusoidal pathological score (r = 0.117, P = 0.261). There was no strong correlation between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r = 0.215, P = 0.037).

Conclusions

It was difficult to predict the degree of chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is necessary to estimate the hepatic functional reserve based on a combination of several clinical indicators without relying on the ICG test, in order to perform a safe radical liver resection.     

Safety and Outcomes Following Resection of Colorectal Liver Metastases in the Era of Current Perioperative Chemotherapy

Background

Preoperative chemotherapy is increasingly utilized in the treatment of colorectal liver metastases (CRLM). Although this strategy may improve resectability, long-term advantages of preoperative chemotherapy for resectable CRLM are less clear. The objective of this study is to report safety and outcomes when perioperative chemotherapy is routinely added to surgery for CRLM.

Methods

A retrospective review of patients undergoing liver resections for CRLM during 2003–2011 in single academic oncology center. Demographic data, tumor characteristics, chemotherapy, surgical details, complications and survival were analyzed.

Results

The study included 157 patients that underwent 168 liver operations. One hundred eighteen patients (70 %) underwent preoperative chemotherapy (75 % oxaliplatin-based). Preoperative portal vein embolization was utilized in 16 (10.1 %) patients. Overall survival (OS) was 89, 57, and 27 % at 1, 3, and 5 years, respectively (median survival—42.8 months). Eleven (7 %) patients had repeat resections for liver recurrence. Thirty-day mortality was 1.26 %, morbidity—24 % (6 %—liver related). Complications were not significantly different in patients that had preoperative chemotherapy. On a multivariate analysis advanced age and >3 lesions predicted poor OS, while advanced age, lesions >5 cm, synchronous lesions, margin-positivity and resection less than hepatectomy were associated with decreased DFS.

Conclusions

Our results suggest that even with chemotherapy and resection only a subset of patients remain disease-free after 5 years. However, even in a high-risk patient with multiple lesions, preoperative chemotherapy can be administered safely without apparent increase in postoperative complications. Perioperative chemotherapy should be considered particularly in patients with multifocal or large lesions, synchronous disease and short disease-free interval.     

Does “Conversion Chemotherapy” Really Improve Survival in Metastatic Colorectal Cancer Patients with Liver-Limited Disease?

Background

The clinical benefits of conversion chemotherapy followed by liver resection for initially unresectable colorectal liver metastases are still controversial. The criteria for unresectability vary from one team to another. To clarify this issue, we retrospectively assessed the survival and characteristics of metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) who underwent conversion therapy.

Method

Our criteria for resectability depended on the size of the remnant liver volume (>30 %) and expected function after removal of all metastases. Between December 2007 and September 2011, a total of 115 patients were diagnosed as having mCRC with LLD and received chemotherapy. Among them, 47 had tumors that were initially diagnosed as resectable. They underwent hepatic resection after chemotherapy (resected group). Of the 67 tumors were initially diagnosed as unresectable, 12 became resectable after chemotherapy (conversion group), leaving 55 tumors that remained unresectable after chemotherapy (unresected group).

Results

The median follow-up was 25.2 months. Hepatic resection was more invasive in the conversion group than in the resected group. Median disease-free survival was significantly higher in the resected group than in the conversion group (p = 0.013). Overall survival (OS) was also higher in the resected group, but the difference was not significant (p = 0.36). However, OS was significantly higher in the conversion group than in the unresected group (p = 0.034). Multivariate analysis of the resected and conversion groups showed that OS was significantly negatively influenced by abnormal carcinoembryonic antigen levels at surgery (p = 0.037) and a hospital stay >30 days (p = 0.009).

Conclusions

Our results showed that conversion chemotherapy could contribute to longer OS in mCRC patients with LLD.     

Colorectal Cancer with Synchronous Resectable Liver Metastases: Monocentric Management in a Hepatobiliary Referral Center Improves Survival Outcomes

Background

Management of patients with synchronous colorectal liver metastases (SCRLM) should be individually tailored. This study compares patients managed by hepatobiliary centers from diagnosis with those referred for liver resection (LR).

Methods

Between 1998 and 2010, a total of 284 patients with SCRLM underwent resection; 106 resectable patients (1–3 unilobar metastases, diameter <100 mm, liver-only disease) were divided into two groups: 66 managed from diagnosis (group A) and 40 referred for LR (group B).

Results

Group A contained a greater proportion of multiple metastases (55.0 vs. 34.8 %, P = 0.042). Group B always received colorectal surgery as up-front treatment (vs. 18.2 %, P < 0.0001). In group B, chemotherapy before LR was more common (72.5 vs. 33.3 %, P = 0.0001) and lasted longer (P = 0.010). More patients in group B exhibited disease progression before LR (17.5 vs. 3.0 %, P = 0.025). Group A underwent fewer surgical procedures (80.3 % simultaneous resection vs. 0 %, P < 0.00001), with similar short-term outcomes. After a median follow-up of 42.0 months, group A exhibited higher 5 year disease-free survival (DFS, 64.8 vs. 30.8 %, P = 0.005) and fewer extrahepatic recurrences (21.5 vs. 47.5 %, P = 0.005). The late-referral group (>6 months, n = 24) had shorter median overall survival (OS) and DFS than group A (49.1 and 25.3 months vs. not achieved and not achieved, P < 0.05). The early-referral group exhibited OS and DFS similar to group A. Multivariate analysis confirmed late referral as a negative predictive factor of OS and DFS.

Conclusions

Monocentric management of SCRLM in hepatobiliary centers is associated with shorter preoperative chemotherapy, better disease control, fewer surgical procedures (simultaneous resection), and, compared with late-referred patients, better survival.     

Response to Preoperative Chemotherapy Predicts Survival in Patients Undergoing Hepatectomy for Liver Metastases from Gastric and Esophageal Cancer

Background

The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM.

Methods

Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated.

Results

Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24 %, respectively. Postoperative morbidity and mortality rates were 32 and 4 %, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9 %, P?=?.005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0 %, P?P?=?.045).

Conclusion

For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.     

Colorectal Liver Metastases Growth in the Embolized and Non-Embolized Liver After Portal Vein Embolization: Influence of Initial Response to Induction Chemotherapy

Purpose

To compare tumor progression in both embolized and non-embolized liver lobes after portal vein embolization (PVE) in patients with bilobar colorectal liver metastases (CLM), according to the initial response to induction chemotherapy.

Methods

From 2002 to 2012, a total of 42 consecutive patients with bilobar CLM initially treated using induction chemotherapy underwent right PVE to achieve adequate future liver remnant volume. Tumoral and liver parenchyma volumes, as well as their volume variations, were measured on computed tomography before and after PVE in both embolized and non-embolized. Patients were classified as fast (≤6 cycles of induction chemotherapy) and slow (>6 cycles) responders.

Results

Overall, 432 metastases were analyzed in 42 patients. Patients were slow responders in 29 (69 %) cases. Tumoral volume increased in 29 (69 %) cases in the embolized liver (+48 %; p < 0.0001), and in 28 (66 %) cases in the non-embolized liver (+31 %; p < 0.0001). Fast responders had a tumoral volume decrease in both embolized (?4 %) and non-embolized (?9 %) lobes. On the opposite side, slow responders had tumoral volume increase in both embolized (+79 %) and non-embolized (+32 %) lobes. On multivariate analysis, a ‘slow’ response to induction chemotherapy was the only factor associated with tumoral progression in both embolized (p = 0.0012) and non-embolized (p = 0.001) lobes.

Conclusion

Tumor growth after PVE is observed in both embolized and non-embolized liver lobes in most patients but is significantly associated with slow response to induction chemotherapy.     

Evaluation of Chemotherapy-Associated Liver Injury in Patients with Colorectal Cancer Liver Metastases Using Indocyanine Green Clearance Testing

Background

Systemic chemotherapy may render initially unresectable colorectal cancer liver metastases resectable. Histopathologic examinations of resected nontumoral liver tissue revealed chemotherapy-associated liver injuries, which was recognized to impair the function of the remnant liver. We therefore evaluated whether indocyanine green (ICG) plasma clearance helps to assess chemotherapy-induced liver damage.

Methods

Data of 101 liver resections performed between 2006 and 2008 for colorectal liver metastases were analyzed for this study. Eighteen patients had liver resection without preoperative treatment, whereas 83 patients underwent neoadjuvant chemotherapy before surgery. ICG clearance was assessed by pulse densitometry before surgery.

Results

Comparison of ICG retention clearances demonstrated that patients pretreated with systemic chemotherapy had a significantly lower plasma disappearance rate (ICG-PDR; 19.3 ± 5.9 vs. 23.1 ± 3.8%/min; P = 0.002) and a significantly elevated ICG retention rate at 15 min (7.9 ± 6.6 vs. 3.8 ± 1.9%; P < 0.001). The percentage of subjects with an abnormal ICG-PDR (≤18%/min) was significantly higher in the pretreated group (48.2% vs. 5.6%; P = 0.001). Patients with an ICG-PDR of ≤18 had a prolonged postoperative hospital stay and experienced four times more complications in their postoperative course.

Conclusions

ICG clearance helps to identify patients with impaired liver function after neoadjuvant chemotherapy and aids in the estimation of the postoperative risk of morbidity after liver resection for colorectal liver metastases.     

Prognostic Impact of Positive Surgical Margins After Resection of Colorectal Cancer Liver Metastases: Reappraisal in the Era of Modern Chemotherapy

Background

The purpose of the present study was to assess the prognostic impact of positive surgical margins (R1) after liver resection (LR) of colorectal liver metastases (CRLM) in the era of modern chemotherapy regimens. R1 resection is a negative prognostic factor after LR of CRLM. The significance of R1 margins in the era of effective chemotherapy is unknown.

Methods

From January 2000 to December 2009, 215 patients (177 men: 62 %; median age 60 years; range 30–84 years) underwent LR of CRLM. The LR was considered R1 (margin <1 mm) in 49 patients (23 %) and R0 in 166 patients (77 %). Overall, 108 (50 %) patients received preoperative chemotherapy and 156 (72 %) patients received postoperative chemotherapy.

Results

With a median follow-up of 36 months (range 1–141 months), the 5-year overall survival (OS) rate (47 vs 40 %; p = 0.05) and the disease-free survival (DFS) rate (36 vs 23 %; p = 0.006) were significantly lower in the R1 group. Recurrence developed in 152 patients (71 %) and the rate of recurrence was significantly higher (84 vs 67 %; p = 0.02) in the R1 group. On multivariate analysis, N+ status of the colorectal primary tumor (p = 0.008), presence of radiologically occult disease (p = 0.04), and R1 resection (p = 0.03) were independent adverse predictors of OS. The N+ status of the primary tumor (p = 0.003) and R1 resection (p = 0.02) were independent adverse predictors of DFS. On multivariate analysis use of postoperative chemotherapy was the only independent predictor of improved DFS (p = 0.02) in the R1 group.

Conclusions

A positive resection margin remains a significant poor prognostic factor after LR of CRLM in the era of modern chemotherapy. Postoperative chemotherapy reduces recurrence rates after R1 resection of CRLM.     

Up-front Hepatic Resection for Metastatic Colorectal Cancer Results in Favorable Long-term Survival

Background

Hepatic metastasis from colorectal cancer (CRC) is best managed with a multimodal approach; however, the optimal timing of liver resection in relation to administration of perioperative chemotherapy remains unclear. Our strategy has been to offer up-front liver resection for patients with resectable hepatic metastases, followed by post–liver resection chemotherapy. We report the outcomes of patients based on this surgical approach.

Methods

A retrospective review of all patients undergoing liver resection for CRC metastases over a 5-year period (2002–2007) was performed. Associations between clinicopathologic factors and survival were evaluated by the Cox proportional hazard method.

Results

A total of 320 patients underwent 336 liver resections. Median follow-up was 40 (range 8–80) months. The majority (n = 195, 60.9 %) had metachronous disease, and most patients (n = 286, 85 %) had a major hepatectomy (>3 segments). Thirty-six patients (11 %) received preoperative chemotherapy, predominantly for downstaging unresectable disease. Ninety-day mortality was 2.1 %, and perioperative morbidity occurred in 68 patients (20.2 %). Actual disease-free survival at 3 and 5 years was 46.2 % and 42 %, respectively. Actual overall survival (OS) at 3 and 5 years was 63.7 % and 55 %, respectively. Multivariate analysis identified four factors that were independently associated with differences in OS (hazard ratio; 95 % confidence interval): size of metastasis >6 cm (2.2; 1.3–3.5), positive lymph node status of the primary CRC (N1 (2.0; 1.0–3.8), N2 (2.4; 1.2–4.9)), synchronous disease (2.1; 1.3–3.5), and treatment with chemotherapy after liver resection (0.42; 0.23–0.75).

Conclusions

Up-front surgery for patients with resectable CRC liver metastases, followed by chemotherapy, can lead to favorable OS.